Second-Line Sacituzumab Tirumotecan Plus Anlotinib for Advanced Driver Gene-Negative Non-Squamous NSCLC

Inclusion Criteria:

1. Age ≥18 years, regardless of gender.
2. Histologically or cytologically confirmed locally advanced (Stage IIIB/IIIC) or metastatic (Stage IV) non-squamous NSCLC, progressing after prior anti-PD-1/L1 monoclonal antibody combined with platinum-based doublet chemotherapy.
3. No known driver gene alterations such as EGFR, ALK, ROS1, NTRK, BRAF, MET, KRAS, HER2, RET, etc.
4. At least one measurable target lesion not previously irradiated, assessed by the investigator per RECIST v1.1.
5. ECOG performance status score of 0 or 1.
6. Asymptomatic or locally treated and stable brain metastases are allowed.
7. Life expectancy ≥ 12 weeks.
8. Adequate organ and bone marrow function.
9. Agreement to use effective medical contraception from signing informed consent until 6 months after the last dose.
10. Voluntary participation, signed informed consent, and ability to comply with the protocol.

Exclusion Criteria:

1. Tumors histologically or cytologically confirmed with mixed small cell lung cancer, squamous cell carcinoma, neuroendocrine carcinoma, or carcinosarcoma components.
2. Prior treatment with TROP2-targeted therapy or any drug targeting topoisomerase I (including ADCs).
3. Known meningeal, brainstem, spinal cord metastases and/or compression, or active central nervous system (CNS) metastases.
4. Other malignancies within 3 years prior to dosing (except locally cured tumors like basal cell carcinoma, squamous cell carcinoma of the skin, cervical carcinoma in situ, etc.).
5. Presence of major cardiovascular diseases or risk factors within 6 months prior to dosing (e.g., myocardial infarction, severe arrhythmias, active myocarditis, major vascular disease requiring surgery).
6. Poorly controlled hypertension (systolic \> 160 mmHg and/or diastolic \> 100 mmHg).
7. History of (non-infectious) interstitial lung disease (ILD) or non-infectious pneumonitis requiring steroid treatment, or current active/suspected ILD/pneumonitis.
8. Documented severe dry eye syndrome, severe meibomian gland disease and/or blepharitis, or corneal disease preventing/delaying healing.
9. Active chronic inflammatory bowel disease, gastrointestinal obstruction, severe ulcer, gastrointestinal perforation, abdominal abscess, or acute gastrointestinal bleeding.
10. Risk of esophageal-tracheal or esophageal-pleural fistula.
11. Tumors invading major blood vessels or high risk of fatal bleeding.
12. Bleeding symptoms or any ≥CTCAE grade 3 bleeding event with unhealed wounds, ulcers, or fractures within 1 month prior to first dose.
13. Known active tuberculosis.
14. History of allogeneic organ transplant or allogeneic hematopoietic stem cell transplant.
15. HIV positive, history of AIDS, or active syphilis infection.
16. Major surgery within 4 weeks prior to dosing or planned major surgery during the study.
17. Current use of strong CYP3A4 inducers (must be avoided at least 3 weeks prior).
18. Live vaccine within 30 days prior to dosing or planned during the study.
19. Pregnant or lactating women.
20. Any condition that, in the investigator's opinion, interferes with the evaluation of the study drug or compromises subject safety.